We have identified sixteen families in which polycystic liver disease occurs in the absence of any evidence of polycystic kidney disease (PLD). Eight of these families have multiple affected individuals consistent with an autosomal dominant pattern of inheritance (ADPLD). The polycystic liver disease observed in these individuals is phenotypically indistinguishable from that seen in ADPKD. We have excluded linkage to either of the known loci for ADPKD in one ADPLD kindred. We hypothesize that ADPLD is under-diagnosed, that ADPLD is an entity distinct from autosomal dominant polycystic kidney disease (ADPKD), that the familial nature of the disorder makes identification of the ADPLD disease gene possible by positional cloning, that such an approach is the most likely means for identifying this gene and that characterization of the ADPLD gene(s) will contribute importantly to the understanding of the pathways involved in cystogenesis in human disease. We propose to undertake: 1) A comprehensive characterization of the clinical phenotype of ADPLD; 2) A molecular genetic characterization of ADPLD families leading to a linkage based localization of the ADPLD gene locus; 3) positional cloning approach to disease gene identification with production of a physical map around the disease gene locus; and 4) Direct analysis of genes from the ADPLD region as a means of identifying the ADPLD gene.